W.M.M.J. Bovée

Retrieval of frequencies, amplitudes, damping factors, and phases from time-domain signals using a linear least-squares procedure

Abstract A new method for quantitative analysis of time-domain signals is reported. It amounts to fitting a function consisting of exponentially damped sinusoids with arbitrary phases to the data. By invoking the principle of linear prediction (LP) the fitting can be carried out by a linear least-squares (LS) procedure, and therefore needs no starting values The LS procedure is based on singular value decomposition (SVD), which enables one to distinguish between signal and noise. The method, denoted by LPSVD, yields a list comprising the frequency, damping factor, amplitude, and phase of each retrieved sinusoid. In addition, LPSVD is insensitive to truncation at the beginning and/or the end of the signal, and in fact is capable to accurately reconstruct the missing part. Preprocessing of the data is not necessary. Finally, the method achieves higher resolution than fast Fourier transformation.

In vitro evaluation of a novel bioreactor based on an integral oxygenator and a spirally wound nonwoven polyester matrix for hepatocyte culture as small aggregates

BACKGROUND/AIMS The development of custom-made bioreactors for use as a bioartificial liver (BAL) is considered to be one of the last challenges on the road to successful temporary extracorporeal liver support therapy. We devised a novel bioreactor (patent pending) which allows individual perfusion of high density cultured hepatocytes with low diffusional gradients, thereby more closely resembling the conditions in the intact liver lobuli. METHODS The bioreactor consists of a spirally wound nonwoven polyester matrix, i.e. a sheet-shaped, three-dimensional framework for hepatocyte immobilization and aggregation, and of integrated hydrophobic hollow-fiber membranes for decentralized oxygen supply and CO2 removal. Medium (plasma in vivo) was perfused through the extrafiber space and therefore in direct hepatocyte contact. Various parameters were assessed over a period of 4 days including galactose elimination, urea synthesis, lidocaine elimination, lactate/pyruvate ratios, amino acid metabolism, pH, the last day being reserved exclusively for determination of protein secretion. RESULTS Microscopic examination of the hepatocytes revealed cytoarchitectural characteristics as found in vivo. The biochemical performance of the bioreactor remained stable over the investigated period. The urea synthesizing capacity of hepatocytes in the bioreactor was twice that of hepatocytes in monolayer cultures. Flow sensitive magnetic resonance imaging (MRI) revealed that the bioreactor construction ensured medium flow through all parts of the device irrespective of its size. CONCLUSIONS The novel bioreactor showed encouraging efficiency. The device is easy to manufacture with scale-up to the liver mass required for possible short-term support of patients in hepatic failure.

Parameter estimation from Rician‐distributed data sets using a maximum likelihood estimator: Application to t1 and perfusion measurements

General expressions are presented to calculate the maximum likelihood (ML) estimator and corresponding Fisher matrix for Rician‐distributed data sets. This estimator results in the most precise, unbiased estimations of T1 from magnitude data sets, even when low signal‐to‐noise ratios (<6) are present. By optimizing the sample point distributions for inversion‐recovery experiments, a 32% increase in precision of the estimated T1 is obtained, compared with a linear sampling scheme. Perfusion rates are estimated from combined data sets of the slice‐ and nonslice‐selective inversion‐recovery experiments, as obtained with the flow‐sensitive alternating inversion recovery (FAIR) technique. The ML estimator for the combined data set results in the most precise, unbiased estimations of the perfusion rate. Error analysis shows that very high signal‐to‐noise ratios are required for precise estimation of perfusion rates from FAIR experiments. Magn Reson Med 41:614–623, 1999.

Quality assessment in in vivo NMR spectroscopy: III. Clinical test objects: Design, construction, and solutions

Based on the requirements of test protocols developed to evaluate clinical MRS single slice and volume localisation sequences, two clinical test objects, STO1 and STO2 have been developed. The properties of a range of potential construction materials have been assessed, demonstrating that the water/Perspex interface produced minimum susceptibility effects. The design of the objects has been evaluated in trials on different magnetic resonance instruments, with size and loading being adjusted to allow use on currently available equipment. Appropriate test solutions for 31P and 1H measurements have been developed and their properties evaluated.

Noninvasive Assessment of the Functional Neovasculature in 9L-Glioma Growing in Rat Brain by Dynamic 1H Magnetic Resonance Imaging of Gadolinium Uptake

Pathophysiologic parameters of the functional neovasculature and the blood-brain barrier of 9L-glioma in rat brain were measured noninvasively by dynamic 1H magnetic resonance imaging studies of gadolinium (Gd)-DTPA uptake. Changes of apparent [Gd-DTPA] uptake in time (CT[t]) were analyzed in a slice through the center of 10 9L-gliomas using fast T1 measurements. The distribution of the contrast agent was spatially correlated with the distribution of perfused microvessels as determined by immunohistochemical analysis. This method permits a distinction between perfused and nonperfused microvessels with a disrupted blood-brain barrier. In transverse slices of the whole tumor, a spatial correlation was observed between CT maps and the two-dimensional distribution of perfused microvessels. In the next step, Gd-DTPA uptake rates were spatially related to the perfused microvessel density (Np) or vascular surface area (Sp). In tumor voxels with perfused microvessels, a linear correlation was found between Gd-DTPA uptake rate constants (k values) and Np or Sp. No correlation was observed between k values and the total microvessel density. These are the first data that show a relation between Gd-DTPA uptake rates and parameters of the functional neovasculature in 9L-glioma growing in rat brain. Now that Gd-DTPA uptake studies can be related to parameters of the functional neovasculature, they may be used more efficiently as a prognostic tool before or during therapy.

Quality assessment in in vivo NMR spectroscopy: IV. A multicentre trial of test objects and protocols for performance assessment in clinical NMR spectroscopy

A multicentre trial of test objects and protocols for performance assessment in single volume and slice selective magnetic resonance spectroscopy (MRS) was conducted by the European Community Concerted Action on MRI and MRS. The trial assessed phosphorus and proton localisation techniques implemented on commercially available MR systems at ten sites in Europe. At each site, a number of parameters devised by the Concerted Action were measured using prototype test objects. Some of these parameters related to the quality of localisation and others to the overall performance of the spectrometer. Results were obtained for the ISIS, DRESS, STEAM, and PRESS sequences with a range of acquisition parameters, allowing evaluation of the assessment methodology and comparison of the efficacy of various implementations of these localisation techniques. The results of this trial have been important in the development of the Concerted Actions final recommendations for MRS performance assessment, and demonstrate that such assessment provides valuable information in the comparison of spectroscopy data from different sites and in the development of new localisation sequences, and provides a means of quality assurance in MRS.

A single-shot localization pulse sequence suited for coils with inhomogeneous RF fields using adiabatic slice-selective RF pulses

RF inhomogeneity affects the localization performance in localized MRS. To study these effects we will concentrate in this contribution on surface coils because they are widely used, provide a simple, easy-to-implement means of localization, and, due to a good filling factor, have a high signal-to-noise ratio (SNR) ( 1, 2). Their strong RF inhomogeneity prevents the use of amplitude-modulated (AM) localization RF pulses for accurate localization. Above a critical RF amplitude threshold adiabatic IZ ?r pulses (n = 1,2,. . .) have the property of rotating magnetization nearly independent of the RF amplitude (3-5 ), which makes them very useful in combination with surface coils. Most localization sequences based on the adiabatic principle [e.g., (6, 7)] are multishot methods. This means that the localized signal is obtained by adding and subtracting the signals originating from the total sample of several independent shots. This has the drawbacks that a large dynamic range of the receiver is needed and that the method is sensitive to motions of the sample and spectrometer instabilities. A different approach is the stimulated-echo sequence presented by Kunz (8)) based on adiabatic r/2 pulses, which allows a 1 D localization. A drawback of using stimulated echoes is the inherent 50% signal loss. In this contribution a single-shot adiabatic 3D localization pulse sequence is proposed which overcomes the above-mentioned problems. For convenience in the remainder of this contribution this method is denoted, SADLOVE (single-shot adiabatic localized volume excitation). With the aid of a two-compartment phantom and a single-turn circular surface coil ( C

Quality assessment in in vivo NMR spectroscopy: II. A protocol for quality assessment: EEC concerted research project

= 10 mm), the localization performance of SADLOVE is tested for uncoupled spin systems. Figure 1 shows the SADLOVE pulse sequence. Directly after the adiabatic 7r/2 pulse, a gradient G, is switched on and a so-called slice-selective phase-compensated 2r pulse (9, 10) is applied for 1D localization. Extension to 2D or 3D localization is effected by adding one or two 27r pulses. If the time between the adiabatic pulses is negligible, acquisition of the FID-like localized signal can start directly after the last 27r pulse because the spins in the volume of interest (VOI) do not undergo a net phase change during the 27r pulses. If this time is not negligible, either a hard a refocusing pulse must be used after the last 27r pulse and the echo sampled, as we did, or the delayed FID is sampled and analyzed by time-domain fitting ( I1 ) to circumvent the problems of phase distortions and baseline roll. A central role in SADLOVE is played by the adiabatic phase-compensated 2a pulse (9, 10). This pulse consists of two identical sech/tanh a pulses B1 (t) = Q0 sech( 8t) ‘+&

In vivo 1H-NMR procedure to determine several rat cerebral metabolite levels simultaneously, undisturbed by water and lipid signals

A protocol has been developed for quality assessment in in vivo NMR spectroscopy (MRS) on whole body and animal systems. The protocol, which has been evaluated in a series of international trials, defines procedures, objects and substances to evaluate the localisation of common slice and volume selection sequences, and to assess other relevant aspects of system performance, including: signal-to-noise; signal loss; relation between signal strength, concentration and volume; selective suppression of spectral lines; spectrometer stability.

Quality assessment in in vivo NMR spectroscopy: VI. Multicentre quantification of MRS test signals

Methods developed for in vivo 1H-NMR spectroscopy are evaluated and applied using conscious rats. Good quality 1H-spectra of the brain are obtained using a surface coil and a spin echo pulse sequence with the binomial 1-1 and 2-2 water suppression pulses. However, comparing spectra from various rats with each other the water and lipid signals, which cause spectral overlap problems, may differ while the other spectral peaks agree well. Spatially one- and two-dimensional 1H spectroscopic imaging of the rat brain shows that the former signals stem from distinct spatial regions localized close to the rf coil. From a spectroscopic image, a spectrum over a limited spatial region is constructed in which the water signals are strongly reduced, the lipid signals are eliminated and lactic acid can be observed clearly simultaneously with other metabolites.